The project is an extension of previous studies on the biochemical events subserving the cerebral dysfunction accompanying neonatal hypothyroidism. Investigations recently completed suggest that thyroid hormones may be implicated in specialized functions of the membrane including the transport of substances that are rate-controlling for cell growth. In general the project is aimed at identifying and characterizing age-dependent interaction of thyroid hormones with subcellular fractions of brain in the rat. Specifically the objectives are to quantitate by radioactive procedures the binding affinities of major cerebral subcellular fractions for thyroid hormones, the existence of specific, physiologically relevant recognition sites in nerve-ending membranes and the changes induced by hypothyroidism during development. Comparisons will be made with plasma membranes isolated from liver tissue. Attention will also be focused on elucidating the nature of the specific binding and identifying the membrane component(s) exhibiting affinity for the hormones.